CXC Chemokine Receptor 4 Antibodies
The CXC chemokine receptor 4 (CXCR4) is the specific receptor for the chemokine CXCL12. CXCR4 plays an essential role for embryonic development of various organ systems, serves as HIV coreceptor, and plays a major role in diseases including cancer and inflammation. The CXCR4 antagonist plerixafor (AMD3100, Mozobil) is an immunostimulant used to mobilize hematopoietic stem cells in cancer patients. In many systems, CXCR4 and ACK3 (previously called CXCR7) cooperate to regulate cell migration. CXCR4 desensitization, β-arrestin recruitment and internalization are regulated by phosphorylation of carboxyl-terminal serine324/serine325 (pS324/pS325-CXCR4) and serine346/serine347 (pS346/pS347-CXCR4) residues. This nomenclature refers to the human CXCR4. This phosphorylation motif is highly conserved across species but corresponds to pS331/pS332-CXCR4 and pS353/pS354-CXCR4 in mice and pS321/pS322-CXCR4 and pS343/pS344-CXCR4 in rats. Agonist-induced CXCR4 phosphorylation is mediated by GRK2, GRK3 and GRK6. Serine346/serine347 is also a substrate for PKC-mediated phosphorylation. For more information on CXCR4 pharmacology please refer to the IUPHAR database. For further reading refer to:
Otte M, Kliewer A, Schütz D, Reimann C, Schulz S, Stumm R. CXCL14 is no direct modulator of CXCR4. FEBS Lett. 2014 Dec 20;588(24):4769-75. doi: 10.1016/j.febslet.2014.11.009. Epub 2014 Nov 18. PubMed PMID: 25451233.
Nakai A, Fujimoto J, Miyata H, Stumm R, Narazaki M, Schulz S, Baba Y, Kumanogoh A, Suzuki K. The COMMD3/8 complex determines GRK6 specificity for chemoattractant receptors. J Exp Med. 2019 Jul 1;216(7):1630-1647. doi: 10.1084/jem.20181494. Epub 2019 May 14. PubMed PMID: 31088898; PubMed Central PMCID: PMC6605747.
Luo J, Busillo JM, Stumm R, Benovic JL. G Protein-Coupled Receptor Kinase 3 and Protein Kinase C Phosphorylate the Distal C-Terminal Tail of the Chemokine Receptor CXCR4 and Mediate Recruitment of β-Arrestin. Mol Pharmacol. 2017 Jun;91(6):554-566. doi: 10.1124/mol.116.106468. Epub 2017 Mar 22. PubMed PMID: 28331048; PubMed Central PMCID: PMC5438129.
Mueller W, Schütz D, Nagel F, Schulz S, Stumm R. Hierarchical organization of multi-site phosphorylation at the CXCR4 C terminus. PLoS One. 2013 May 29;8(5):e64975. doi: 10.1371/journal.pone.0064975. Print 2013. PubMed PMID: 23734232; PubMed Central PMCID: PMC3666969.